title: Effect of a selective rise in sinusoidal norepinephrine on HGP is due to an increase in glycogenolysis.
abstract: To determine the effect of a selective rise in liver sinusoidal norepinephrine (NE) on hepatic glucose production (HGP), norepinephrine (50 ng.kg-1.min-1) was infused intraportally (Po-NE) for 3 h into five 18-h-fasted conscious dogs with a pancreatic clamp. In the control protocol, NE (0.2 ng.kg-1.min-1) and glucose were infused peripherally to match the arterial NE and blood glucose levels in the Po-NE group. Hepatic sinusoidal NE levels rose approximately 30-fold in the Po-NE group but did not change in the control group. The arterial NE levels did not change significantly in either group. During the portal NE infusion, HGP increased from 1.9 +/- 0.2 to 3.5 +/- 0.4 mg.kg-1.min-1 (15 min; P < 0.05) and then gradually fell to 2.4 +/- 0.4 mg.kg-1.min-1 by 3 h. HGP in the control group did not change (2.0 +/- 0.2 to 2.0 +/- 0.2 mg.kg-1.min-1) for 15 min but then gradually fell to 1.1 +/- 0.2 mg.kg-1.min-1 by the end of the study. Because the fall in HGP from 15 min on was parallel in the two groups, the effect of NE on HGP (the difference between HGP in the two groups) did not decline over time. Gluconeogenesis did not change significantly in either group. In conclusion, elevation in hepatic sinusoidal NE significantly increases HGP by selectively stimulating glycogenolysis. Compared with the previously determined effects of epinephrine or glucagon on HGP, the effect of NE is, on a molar basis, less potent but more sustained over time.
authors.affiliation: Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-0615, USA.
authors.forename: C A
authors.initials: CA
authors.lastname: Chu
authors.forename: D K
authors.initials: DK
authors.lastname: Sindelar
authors.forename: D W
authors.initials: DW
authors.lastname: Neal
authors.forename: E J
authors.initials: EJ
authors.lastname: Allen
authors.forename: E P
authors.initials: EP
authors.lastname: Donahue
authors.forename: A D
authors.initials: AD
authors.lastname: Cherrington
mesh_terms: D000596:Amino Acids / Q000097:blood; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D004285:Dogs; D004837:Epinephrine / Q000097:blood; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D005934:Glucagon / Q000097:blood; D005943:Gluconeogenesis / Q000187:drug effects*; D005947:Glucose / Q000008:administration & dosage / Q000494:pharmacology; D005990:Glycerol / Q000097:blood; D007262:Infusions, Intravenous; D007328:Insulin / Q000097:blood; D007700:Kinetics; D007773:Lactates / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008112:Liver Glycogen / Q000378:metabolism*; D008297:Male; D009638:Norepinephrine / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D010179:Pancreas / Q000502:physiology; D011168:Portal System
chemical_list: D000596:Amino Acids; D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D007773:Lactates; D008112:Liver Glycogen; D005934:Glucagon; D005947:Glucose; D005990:Glycerol; D009638:Norepinephrine; D004837:Epinephrine